European Journal of Cardiovascular Medicine

Thrombocytopenia is defined as the platelet count below 1,50,000/µl. It is a common reason to consult a physician in both the inpatient and outpatient setting. Major pathophysiological mechanisms of thrombocytopenia are decreased production, accelerated destruction and splenic sequestration.¹ For the evaluation of thrombocytopenia, a good clinic history and physical examination with basic laboratory tests are essential.

Various infections like Dengue, Malaria, Enteric fever,Scrub typhus, Viral Hepatitis, chikungunya, HIV, are commonly associated with thrombocytopenia. Thrombocytopenia is characterized by bleeding most often from small vessels. Mucosal bleeding is the most common bleeding manifestations in patients with thrombocytopenia. Intracranial bleed is a very rare (<2%) but a dangerous consequence.²

Patients with mild thrombocytopenia are not expected to bleed even with major surgery. In patients with very severe thrombocytopenia, spontaneous bleeding is observed and there is a risk of serious bleeding at values lower than 10,000/µL. Thrombocytopenia has a direct relation with mortality and morbidity in various febrile illnesses.^3,4 Serial monitoring of platelet counts has prognostic value.

The study was a hospital based observational, descriptive analysis and was conducted in the Department of Medicine in MDM Hospital, Jodhpur. A total number of 310 cases having pyrexia with thrombocytopenia were studied. Investigations including complete blood count with peripheral blood smear, liver function test, renal function test, urine routine and microscopy examination, MP by slide, serological test and blood cultures for typhoid fever, NS1Ag and serology tests for dengue(IgM, IgG by ELISA), scrub typhus (IgM), HIV, hepatitis B and hepatitis C were carried out. Thrombocytopenia was classified as Mild (1,00,000-1,50,000/µl), Moderate (51,000-1,00,000/µl) , Severe (20,000-50,000/µl) and Very severe (< 20,000/µl).

The study revealed that majority (37.4%) of patients were in age group of 21 to 30 years. 65.2% were males and 34.2% were females.

All (100%) patients had fever. Maximum number (59.7%) of patients had fever for less than 7 days. Patients with duration of fever for 3 weeks or more were only 1.9% (Figure 1).

154(49.7%) had no bleeding whereas 156(50.3%) patients presented with varied bleeding manifestations. Figure 2 shows that amongst the patients who had bleeding, petechial rash was the most common, found in 48(15.5%) cases, followed by epistaxis in 28(9.4%), melena in 25(8.0%) and bleeding per vagina in 15(4.8%) patients. The most serious bleeding manifestation was intracranial bleed and it was observed in 2(0.65%) patients.

Myalgia was the commonest symptom in 87 (28.1%) patients other than fever and bleeding followed by headache in 46 (14.8%) patients, vomiting in 38 (12.3%) patients, abdominal pain in 29 (9.4%) patients, shortness of breath in 23 (7.4%), loose stool in 20 (6.5%) and cough in 20 (6.5%) patients. 14 (4.5%) patients were presented with altered sensorium.

Mild thrombocytopenia was seen in 3.9% patients, 25.8% patients had moderate and 47.1% had severe thrombocytopenia whereas 23.2% had very severe thrombocytopenia at the time of presentation (figure 3).

The most common ultrasound abdomen finding was peri gall bladder oedema, present in 75 (24.2%) patients followed by ascites in 48 (15.5%), splenomegaly in 41 (13.2%) patients and hepatosplenomegaly in 31 (10%) patients. Liver abscess was found in 3 (1.0%) patients.

Dengue fever was found to be the most common cause of thrombocytopenia, detected in 50.60% cases followed by malaria in 17.1%, scrub typhus in 16.1%, HIV in 4.5%, sepsis in 2.9%, enteric fever in 2.6% and 3.3% cases remained undiagnosed   as PUO. Out of 53 cases of malaria, P.vivax malaria was found in 52.8% cases, P.falciparum malaria was found in 34% cases and mixed infection was found in 13.2% cases. Out of 9 cases of sepsis, urinary tract infection was present in 5, liver abscess in 3 and pneumonia in 1 case (figure 4).

Concomitant infection like dengue fever and scrub typhus was detected in 9 patients, malaria and dengue fever in 7 and scrub typhus and malaria in 3 patients. (Table 1)      

Leukopenia was the most common association other than thrombocytopenia, found in 32.9% patients followed by anemia, seen in 25.1% patients while hyperbilirubinemia and acute kidney injury were seen in 21.3% and 20.3% patients respectively. Hypotension was detected in 12.9% patients. 4.5% patients were presented with altered mental status and the causes were cerebral malaria, tubercular meningitis, sepsis and HIV.

96.5% patients improved with treatment but 3.5% patients succumbed to death. Overall mortality was higher in patients with very severe thrombocytopenia at presentation, patients of P. falciparum malaria, scrub typhus and patients having concomitant infections.

Out of the 72 patients with very severe thrombocytopenia, 62(86.1%) patients had bleeding manifestation. Out of 146 patients with severe thrombocytopenia, 72 (49.3%) patients had bleeding manifestations. 14 (17.5%) patients had bleeding manifestation out of 80 patients of moderate thrombocytopenia and 8 (66.6%) had bleeding manifestation out of 12 patients having mild thrombocytopenia. (Figure 5)

In this study, the mean age of patients was 31.6±12.8 years. Male predominance was observed in our study as 65.2% were males and 34.2% were females.

We observed various bleeding manifestations in patients presented with thrombocytopenia. 49.7% patients had no bleeding whereas 50.3% patients who presented with various bleeding manifestations, petechial rash was the most common, found in 15.5% cases followed by epistaxis (9.4%), melena (8.0%) and bleeding per vagina 4.8% patients. Most serious bleeding manifestation like intracranial bleed was observed in 0.65% patients. Gandhi AA et al⁵, in her study, found that 69 out of 112 patients (60.2%) were presented with some bleeding manifestation and petechial rash (17%) was most common.  

The mean platelet count of the study population at the time of presentation was 45,000 ±58,800/µl. 23.2% patients had very severe thrombocytopenia and 47.1% had severe thrombocytopenia. 25.8% patients had moderate thrombocytopenia and mild thrombocytopenia was seen in 3.9% patients. This result was comparable with study conducted by Nazeer Ahmed et al⁶. He found 19% of patients had very severe thrombocytopenia, 43% had severe thrombocytopenia, 32% of patients with moderate thrombocytopenia and mild thrombocytopenia was seen in 6%.

All cases of thrombocytopenia with evidence of infection were analysed for underlying cause. Amongst them 50.9% patients were diagnosed as dengue fever, 17.1% as malaria, scrub typhus in 16.1% patients whereas HIV was detected in 4.5% patients. Sepsis due to UTI, pneumonia and liver abscess was the cause for thrombocytopenia in only2.9% patients. Enteric fever was detected in 2.6% cases, hepatitis B in 1.6% cases and hepatitis C in 1.0%. In 3.3% patients, no established cause was found. Out of 53 malaria cases, 33.96% had P. Falciparum malaria, 52.83% had P. Vivax malaria and 13.21% had mixed (P. Falciparum + P. Vivax). Mixed infection like dengue fever along with scrub typhus was seen in 9 (2.9%) patients, dengue fever and malaria in 7 (2.3%) and malaria with scrub typhus was detected in 3 (1%) patients.

Shruti Bhalara et al⁷ in her study found dengue fever as most common (28%) aetiology of thrombocytopenia with fever followed by malaria in 22%, septicemia in 6% and haematological malignancy in 1.5%. Dash H S et al⁸ in his study found malaria as most common aetiology (45%) followed by dengue fever in 20%, sepsis in 21%, enteric fever in 10%, haematological malignancy in 2%. Patil P et al⁹ also found malaria as most common (54%) cause followed by dengue fever 15%.

Platelet count at presentation was correlated with bleeding manifestation. Out of 72 patients with very severe thrombocytopenia at presentation, 62(86.1%) had bleeding manifestations. Out of 146 patients with severe thrombocytopenia, 72 (49.3%) patients had bleeding manifestations. 14 (17.5%) patients had bleeding manifestations out of 80 patients with moderate thrombocytopenia. 12 patients had mild thrombocytopenia, out of which 8 (66.6%) had bleeding manifestations. Gandhi AA et al⁵ had correlated bleeding manifestation with that of platelet count at the time of presentation. She found that out of 15 patients with very severe thrombocytopenia, 12.5% had some bleeding manifestation, out of 33 patients with severe thrombocytopenia, 24.11% were having bleeding manifestation and 2% of patients out of 64 patients with moderate thrombocytopenia had some bleeding manifestation.

96.5% patients improved with treatment but 11 (3.5%) patients succumbed to death. Overall mortality was higher in patients with very severe thrombocytopenia at presentation and in patients of P.falciparum malaria, scrub typhus and patients having multiple co-infections. Mortality (3.5%) in our study was comparable with that of mortality (5%) in study done by Patil P et al⁹ whereas mortality (22%) in study conducted by Dash HS et al⁸ was higher.

Pyrexia with thrombocytopenia is a commonly encountered problem with a significant social infliction. In most patients, the cause of the thrombocytopenia can be identified and treated. In this study, dengue fever was the most common infection associated with thrombocytopenia followed by Malaria and Scrub typhus. Severe thrombocytopenia was seen most frequently in 47.1% patients at the time of presentation. Bleeding manifestations occurred in about half of total cases studied and petechial rash was the most common amongst them. Majority of patients improved following treatment, however mortality was higher in patients with very severe thrombocytopenia at presentation and in patients of P. falciparum malaria, scrub typhus and those having concurrent infections.